Apparatuses, indicators, methods and kits with timed color change indication

ABSTRACT

An apparatus, method and kit includes one or more use protocol indicators having a color changeable dye, the dye being translucent or having a first color upon immediate exposure to an environment and for a defined time thereafter and the dye changing color after exposure to the environment for the defined time. A dual environment indicator includes a first indicator color changeable dye being translucent or having a first color upon immediate exposure to a first environment and changing color after exposure to a second environment and a second indicator color changeable dye being translucent or having a first color upon immediate exposure to the second environment and for a defined time thereafter and changing color after exposure to the second environment for the defined time. A time exposure indicator comprises at least one color changeable dye disposed to change color in a sequential manner.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/038,586 (now allowed), which was filed Sep. 26, 2013, entitled“Apparatuses, Indicators, Methods and Kits with Timed Color ChangeIndication”. This application is hereby incorporated by reference in itsentirety.

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

FIELD OF THE INVENTION

Generally speaking, the present application relates to a colorchangeable indicator that changes color after being exposed to aparticular environment for a predetermined period of time. In oneembodiment, the color changeable indicator is intended for use on or indisposable, limited or restricted use products that can transmitcontaminants or disease to a person, cause infection, or decline inquality or potency if reused or used beyond a recommended period oftime. In another embodiment, the color changeable indicator is intendedfor use on or in packaging for a product for human consumption whereinthe product for human consumption can decline in freshness, quality oftaste, and/or potency and/or can cause disease if consumed beyond arecommended period of time. The color changeable indicator acts toindicate that a product should no longer be used or consumed.

More specifically, one embodiment of the present application relates todisposable, limited or restricted use product having multiple useprotocols which affect the lifespan of the product. The presentapplication deals with use protocol indicators having a color changeabledye that changes color after exposure to a particular environment for adefined time. The defined time corresponds to, for example, theexpiration time for a disposable, limited or restricted use product fora particular protocol(s) or the time after which a product should nolonger be used or consumed.

More specifically, another embodiment of the present application relatesto an exposure time indicator that uses a color changeable dye ormultiple color changeable dyes that change color after exposure to anenvironment in a sequential manner. The exposure time indicator createsa spectrum that allows the user to see how much of the product's usefullife has been used and how much remains.

BACKGROUND OF THE INVENTION

Many products currently marketed and sold to consumers are designed forlimited use. These products are usually associated with a single event,a restricted time period or restricted access. There are many reasonsfor the need of single use or limited use products.

An example of a single use product is a disposable syringe. Instrumentcontamination and cross infection between patients is an ever presentconcern if the syringe is inadvertently reused. It is a particularconcern in some countries where repeated use of instruments is known totransmit serious diseases such as HIV and hepatitis. Medical andophthalmic devices that must be sterilized such as scalpels ortonometers (for the measurement of a patient's intraocular pressure) andbody piercing and tattooing instruments used on multiple clients alsogive cause for concern. Needles used in acupuncture offer anotherexample. Decontamination procedures or employment of single-use devicesare methods used to control cross infection, but they rely on personnelawareness, willingness to follow protocol, monitoring and documentation.

The limited use type of product is usually associated with goods thatshould be used for a restricted time period. One example of this type ofproduct is “daily wear” or disposable contact lenses. Contact lenses forrefractive correction or cosmetic purposes require suitable wear andcare regimes in order to maintain good eye health. Non-compliance on thepart of the patient, either through choice or due to lack of education,can injure the eye. Frequent replacement lenses are sometimes worn forlonger than recommended or they may be stored or cleanedinappropriately.

Other examples of limited use products that have a shelf life afterwhich they should not be used because of a risk of infection or adecrease in effectiveness are cosmetic products, personal hygieneproducts such as electric toothbrush heads, and home diagnostic kitssuch as pregnancy tests and ovulation prediction tests. For example, ithas been found that cosmetic applicators can harbor bacteria that caninfect the eye and should be disposed of prior to their expiration toprevent eye infections.

Many products currently marketed and sold to consumers are suppliedprepackaged where the packaging is intended to preserve the freshness ofthe product such as food or beverages or in the case of medication, thepotency of the content within the packaging. These products are usuallyassociated with a single event, i.e., the contents remain fresh orpotent until the packaging is opened by the consumer; however, thefreshness or quality of the contents may decrease over time.

An example of the importance of preservation of a packaged product is acold tablet or a food item. Medicinal potency or food spoilage and theexpense related to these issues are important to both consumers andmanufacturers. Pharmaceuticals, food stuff, and similar items arecommonly packaged in sealed plastic containers.

Gas, such as oxygen, permeation through the plastic material of thecontainer negatively affects the freshness or quality of the contents ofmany packaged products. In the case of pharmaceuticals, oxygenabsorption decreases potency. In the case of food products, oxygenabsorption into the packaged food makes the food taste stale.

Products may have different intended uses and may have different timesafter which the product should no longer be used based on the intendeduse. For example, a single medical device could have many different useprotocols. Depending on the use protocol, the medical device should bechanged after a different period of time. For example, a catheter couldbe used in one way where it should be changed after 72 hours but whenused another way would not need to be changed until 96 or 168 hours.Medications could also have a different shelf life based on differentuses. For example, maximum potency might be required for a certain usewhile a decline in potency would be acceptable for an alternate use.Foods could similarly have a different shelf life based on theirintended use. The same food product might be deemed acceptable forconsumption by a pet longer than it would be deemed acceptable forconsumption by a human.

BRIEF SUMMARY OF THE INVENTION

The present application relates to a color changeable dye that changescolor after being exposed to a particular environment for apredetermined period of time.

In one embodiment of the present application, an apparatus with colorchange indication comprises a disposable, limited or restricted useproduct having more than one use protocol and at least oneinterchangeable use protocol indicator having a color changeable dye,the dye being translucent or having a first color upon immediateexposure to an environment and for a defined time thereafter and the dyechanging color after exposure to the environment for the defined time.

The environment can be an oxygen containing environment and said colorchangeable dye is an oxygen sensing color changeable dye. Theenvironment can be a carbon dioxide containing environment and saidcolor changeable dye can be a carbon dioxide sensing color changeabledye. The environment can be a carbon dioxide containing environment andsaid color changeable dye can be an oxygen sensing color changeable dye.

The at least one interchangeable use protocol indicator can beincorporated into the disposable, limited or restricted use product. Forexample, the at least one interchangeable use protocol indicator cabhave a capillary with the color changeable dye incorporated therein. Theat least one interchangeable use protocol indicator can be disposed onthe disposable, limited or restricted use product. The at least one useprotocol indicator can be provided with the disposable, limited orrestricted use product.

The at least one interchangeable use protocol indicator can be anexposure time indicator.

In another embodiment of the present application, an apparatus having acolor change indicator comprises a first indicator color changeable dye,the dye being translucent or having a first color upon immediateexposure to a first environment and the dye changing color afterexposure to a second environment; and a second indicator colorchangeable dye, the dye being translucent or having a first color uponimmediate exposure to the second environment and for a defined timethereafter and the dye changing color after exposure to the secondenvironment for the defined time. The first environment can be carbondioxide or inert gas and the second environment can be atmosphericoxygen. The indicator can be an exposure time indicator.

In yet another embodiment of the invention, an apparatus with colorchange indication comprises an exposure time indicator comprising atleast one color changeable dye, wherein the at least one colorchangeable dye is disposed to change color in a sequential manner. Theat least one color changeable dye can be translucent or have a firstcolor upon immediate exposure to an environment and change color afterexposure to the environment. The exposure time indicator can have afirst region of the color changeable dye changes color after a firsttime, consecutive regions of the color changeable dye change color atincreasing time intervals after the first time and a final regionchanges color after a final defined time. The final defined time cancorrespond to an expiration time for a disposable, limited or restricteduse product.

The environment can be an oxygen containing environment and said colorchangeable dye can be an oxygen sensing color changeable dye. Theenvironment can be a carbon dioxide containing environment and saidcolor changeable dye can be a carbon dioxide sensing color changeabledye.

The exposure time indicator can be incorporated into a disposable,limited or restricted use product. For example, the exposure timeindicator can be a capillary with the color changeable dye incorporatedtherein. The exposure time indictor can be disposed on a disposable,limited or restricted use product.

The exposure time indicator can have barrier layers over the regions ofcolor changeable dye to achieve the sequential color change.

In yet another embodiment of the present application, a method of usingan apparatus with color change indication comprises providing adisposable, limited or restricted use product having more than one useprotocol said more than one use protocols having an associated useprotocol indicator with a color changeable dye, the dye beingtranslucent or having a first color upon immediate exposure to anenvironment and for a defined time thereafter and the dye changing colorafter exposure to the environment for the defined time; and selecting atleast one use protocol indicator.

In yet another embodiment of the present invention, a kit comprises morethan one use protocol indicator having a color changeable dye, the dyebeing translucent or having a first color upon immediate exposure to anenvironment and for a defined time thereafter and the dye changing colorafter exposure to the environment for the defined time wherein said morethan one use protocol indicators have different defined times. The kitfurther can include a disposable, limited or restricted use product. Theuse protocol indicators can be adhesive use protocol indicators.

These and other advantages and novel features of the present invention,as well as details of illustrated embodiments thereof will be more fullyunderstood from the following description of the drawings.

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 is a schematic drawing of one embodiment of the present inventionshowing a medical device having an interchangeable use protocolindicator incorporated therein.

FIG. 2 is a schematic drawing of one embodiment of the present inventionshowing a capillary containing a color changeable dye.

FIG. 3 is a schematic drawing of one embodiment of the present inventionshowing adhesive interchangeable use protocol indicators for use with amedical device.

FIG. 4 is a schematic drawing of one embodiment of the present inventionshowing an exposure time indicator with a color changeable dye thatchanges color after exposure to an environment in a sequential manner

FIG. 5A-5L are photographs of an exposure time indicator with a colorchangeable dye that changes color after exposure to an environment in asequential manner.

The foregoing summary, as well as the following detailed description ofcertain embodiments of the present application, will be betterunderstood when read in conjunction with the appended drawings. For thepurposes of illustration, certain embodiments are shown in the drawings.It should be understood, however, that the claims are not limited to thearrangements and instrumentality shown in the attached drawings.Furthermore, the appearance shown in the drawings is one of manyornamental appearances that can be employed to achieve the statedfunctions of the system.

DETAILED DESCRIPTION OF THE INVENTION

In accordance with the present invention, a color change indication on aproduct provides accurate information or a warning to a user of: prioruse of a single use product or instrument; a reminder that a limited useproduct has reached its expiration time; or that a product that isrestricted for use has been tampered with. The warning indication isprovided by a dye that changes color in a time controlled manner. Thedye can be disposed on the product itself by being either printed on theproduct or incorporated into the product or within the material forminga portion of the product. The dye can also be disposed on orincorporated into a packaging or other article that accompanies theproduct. The product is then subsequently packaged to provide a sterileenvironment for the product or limited access thereto. The internalatmosphere of the package is an inert gas, carbon dioxide, or a vacuumsuch that the package provides a sealed environment free of substancesthat trigger the color change of the dye, such as oxygen, carbondioxide, nitrogen, water, etc. When the package is subsequently openedand the product is exposed to a trigger substance, such as atmosphericoxygen, the dye disposed on the product will change from a first color(often translucent or somewhat translucent, i.e. a milky white or “waterwhite”) to a second color (often a blue or red color) after a period oftime that is controlled by the composition of the dye and other factorsas discussed in detail below, and that is selected to correspond to thetypical time for a single use of a product in the case of single useproducts or that corresponds to the expiration time of the product. Thetime at which the dye changes color can also be selected so as toindicate that the product may have been tampered with.

Prior patents and applications co-owned by applicant have dealt with theuse of color changeable dyes. U.S. Pat. No. 8,388,131 presented adisposable limited or restricted use apparatus that includes a colorchangeable portion wherein the time that the color change occurs iscontrolled so that it coincides to the approximate time of the end ofone use of a single use apparatus or to the approximate expiration timefor extended but limited or restricted use apparatus. U.S. Pub. No.2013/0150785 presented a color changeable dye including a redoxindicator to create a color change indication on a product that providesaccurate information or a warning to a user of, e.g.: prior use of asingle use product or instrument; a reminder that a limited use producthas reached its expiration time; or that a product that is restrictedfor use has been tampered with. U.S. Pat. No. 8,388,131 and its relatedcases (e.g. U.S. Pub. No. 2013/0088683, U.S. application Ser. No.13/780,050 and U.S. application Ser. No. 13/795,343) and U.S. Pub. No.2013/0150785 are incorporated herein in their entirety by reference.

The present application further addresses disposable, limited orrestricted use products with multiple use protocols. For example, amedical device such as a catheter may have multiple different proceduresfor which it can be used. The time after which the medical devicereaches its expiration may be different depending on the procedure forwhich it is being used. For example, a connector or adapter may be usedin one use protocol in conjunction with a medical device deliveringoncology medication where the device should only be used for a singledose, e.g., around six hours. The connector or adapter couldalternatively be used in a second use protocol with a catheter thatdelivers drugs for an infection over a period 96 hours. The connector oradapter could alternatively be used in a third use protocol with amedical device that delivers insulin therapy to a patient over 168hours. The present application offers a use protocol indicator thatutilizes a color changeable dye to indicate the time after which adisposable, limited or restricted use product should no longer be usedfor a specific use protocol. In such an embodiment, an apparatus withcolor change indication comprises a disposable, limited or restricteduse product and at least one interchangeable use protocol indicator.

The disposable, limited or restricted use product has at least one useprotocol. More commonly, the disposable, limited or restricted useproduct has more than one use protocol. For example, a disposable,limited or restricted use product could have 2, 3, 4, 5, 6, 7, 8, 9, 10,11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, or more useprotocols. Each use protocol has a defined time after which thedisposable, limited or restricted use product should not be used when ithas been used for that particular use protocol. For example, the medicaldevice could have one use protocol for which it should not be used afterexposure to oxygen for 72 hours, it could have a second use protocolafter which it should not be used after exposure to oxygen for 96 hours,a third use protocol after which it should not be used after exposure tooxygen for 168 hours and a fourth use protocol after which it should notbe used after a week. As another example, the medical device could haveone use protocol for which it should not be used after exposure tooxygen for 6 hours, it could have a second use protocol after which itshould not be used after exposure to oxygen for 12 hours, a third useprotocol after which it should not be used after exposure to oxygen for90 hours and a fourth after which it should not be used after 120 hours.

The interchangeable use protocol indicator has a color changeable dye.The color changeable dye is translucent, water white or a first colorupon immediate exposure to an environment and for a defined timethereafter. The dye changes color after exposure to the environment forthe defined time which corresponds to a time after which the disposable,limited or restricted use product should not be used for a particularuse protocol. Where there are multiple use protocols for the disposable,limited or restricted use product there can be multiple interchangeableuse protocol indicators. The indicator may be interchangeable such thata single indicator is adapted such that it may be used with multipledifferent products or different indicators can be used with a singleproduct. The multiple use protocol indicators can have color changeabledyes such that the defined time after which the color changeable dyeschange corresponds to the expiration time for the disposable, limited orrestricted use product for a particular use protocol. For example, themedical device discussed above with use protocols for which it shouldnot be used after exposure to oxygen for 72 hours, 96 hours and 168hours could have three use protocol indicators with color changeabledyes that change after exposure to oxygen for 72 hours, 96 hours and 168hours respectively. The expiration time for a disposable, limited orrestricted use product can be the time after which the manufacturerrecommends replacement, the time after which the product will decline inquality, potency or effectiveness and/or the time after which theproduct could be dangerous to use.

The color changeable dye can be varied in order to change color inresponse to a variety of different environments for a defined time. In apreferred embodiment, the environment is an oxygen containingenvironment and the color changeable dye is an oxygen (O2) sensing colorchangeable dye. In another preferred embodiment, the environment is acarbon dioxide containing environment and the color changeable dye is acarbon dioxide (CO2) sensing color changeable dye. In another preferredembodiment, the indicator with an oxygen or carbon dioxide sensing colorchangeable dye is contained within a carbon dioxide rich environment andlater exposed to an atmospheric oxygen environment. In another preferredembodiment, the indicator with a carbon dioxide sensing color changeabledye is contained within an oxygen rich environment and later exposed toa carbon dioxide rich environment. In another preferred embodiment, theindicator with an oxygen or carbon dioxide sensing color changeable dyeis contained within an inert gas environment and later exposed to anatmospheric oxygen or carbon dioxide environment. The environment towhich the color changeable dye responds can be chosen based on theparticular use protocol. For example, a medical device could have oneuse protocol for which it should not be used after exposure to oxygenfor 1 hour, it could have a second use protocol after which it shouldnot be used after exposure to oxygen for 8 hours and a third useprotocol after which it should not be used after exposure to carbondioxide for 20 minutes. The color changeable dye for the associatedinterchangeable use protocol indicators could be selected accordinglysuch that the color changeable dyes on the three use protocol indicatorschange after exposure to oxygen for 1 hour, exposure to oxygen for 8hours and exposure to carbon dioxide for 20 minutes respectively.

The color change indicator may include a first indicator colorchangeable dye, the dye being translucent or having a first color uponimmediate exposure to a first environment (such as carbon dioxide orinert gas) and the dye changing color after exposure to a secondenvironment (such as atmospheric oxygen); and a second indicator colorchangeable dye the dye being translucent or having a first color uponimmediate exposure to the second environment and for a defined timethereafter and the dye changing color after exposure to the secondenvironment for the defined time. As one embodiment, an indicator mayinclude a first indicator dye and a second indicator dye such that thefirst indicator dye indicates a packaging condition and the secondindicator dye is associated with a use protocol. For example, anindicator may include a carbon dioxide sensing dye and an oxygen sensingdye where the indicator is packaged within in a carbon dioxide richenvironment which triggers the carbon dioxide sensing dye, indicatingthat the package is sealed. When the indicator is subsequently removedfrom the package, the oxygen sensing dye will serve as a use protocolindicator in accordance with the present invention. Moreover, theindicator may be an exposure time indicator as described below.

In order to create dyes that change color after exposure to differentenvironments after different periods of time there are a number ofpossible approaches. Dyes that have completely different compositionscan be used. Variations in the makeup of the dye can be used.Scavengers, such as oxygen scavengers, can be added. Chemical orphysical barriers can be also be added. Some examples of colorchangeable dyes using these approaches to achieve color change atdifferent times or in response to different atmospheres are discussedbelow.

Examples of oxygen sensing color changeable dyes with various times ofcolor change are discussed in U.S. Pat. No. 8,388,131 and its relatedcases (e.g. U.S. Pub. No. 2013/0088683, U.S. application Ser. No.13/780,050 and U.S. application Ser. No. 13/795,343). For applicationswhere the dye is required to be substantially translucent and whereinthe dye is to change color after exposure to atmospheric oxygen afterapproximately 5-10 minutes, the dye solution may be formed as follows.Approximately 12 grams of glucose is added to 600 cc of distilledde-ionized water. Next, approximately 12 grams of sodium hydroxide isadded to the mixture. To this mixture is added 10 cc of a Methylene Bluesolution prepared by mixing 0.1 gram of Methylene Blue in 100 cc ofethanol where the ethanol evaporates in the drying process. Thereafter,60 grams of methyl cellulose is added to the mixture. Alternatively,E414 acacia gum may be substituted for the methyl cellulose. This dyesolution will change from translucent to blue in a short amount of timeafter the packaging is opened and the product on which the dye isdisposed is exposed to oxygen. If the color change desired is fromsubstantially translucent to a red color, 10 cc of a Safranine Tsolution can be substituted for the Methylene Blue solution. TheSafranine T solution is prepared by mixing 0.3 grams of Safranine T with10 ml of ethanol.

In order to delay the time at which the dye changes color upon exposureto oxygen, Iron (II) carbonate can be added to the above dye solution.For example, 0.1 grams of Iron (II) carbonate can be added to a 3 mlquantity of the above dye solution forms a dye that will change color toeither blue or red after approximately 9-10 minutes of exposure toatmospheric oxygen. By increasing or decreasing the amount of Iron (II)carbonate the time that it takes for the color change to occur uponexposure to oxygen can be respectively increased or decreased. It isnoted that, the addition of the Iron (II) carbonate will change the dyefrom being substantially translucent to somewhat translucent or a faint,milky white known as “water white” wherein the translucency diminishesas more Iron (II) carbonate is added.

If it is desired that the color change takes substantially longer than10 minutes at atmospheric oxygen, for example, 12-16 hours atatmospheric oxygen, 0.5 grams of Iron (II) carbonate is added to a 3 mlquantity of the dye solution instead of 0.1 grams of Iron (II)carbonate. It is noted that the Iron (II) carbonate acts as an oxygenscavenger in the dye solution that preferentially absorbs oxygen,converting to Iron (III) carbonate. When the Iron (II) carbonate iscompletely converted to Iron (III) carbonate, the oxygen in theenvironment reacts with the color changeable dye so that the dye changesto blue or red and becomes visible.

In order to prevent the dye from changing color until an even longertime has passed, wax can be added to the dye solution. To provide acolor change indication on a product after approximately 1500 hours atatmospheric oxygen, the oxygen diffusion rate through the dye solutioncan be lowered or decreased by the addition of wax as follows.Specifically, when 0.3 cc of beeswax is added to a 3 ml quantity of thedye described above, the color change is delayed by approximately tenhours at atmospheric oxygen for a volume of dye of 0.01 mm3. This amountof dye can be used in an area of approximately 2 mm in height and 20 mmlong on a product. With the addition of 0.6 cc beeswax to the dyesolution, the color change can be delayed to approximately 100 hours atatmospheric oxygen. To further extend the time that it takes for thecolor change to approximately 1500 hours at atmospheric oxygen, 0.7grams of Iron (II) carbonate can be added to the dye solution and waxmixture.

Examples of color changeable dyes including dyes incorporating redoxindicators are discussed in U.S. Pub. No. 2013/0150785. That applicationdiscusses a color changeable dye of the that may include a redoxindicator, a reduction reaction initiator, an electron donor, oxygenscavenger, an indicator barrier agent, an agent to facilitate mixing anda thickening agent wherein the color changeable dye changes to a warningcolor after exposure to oxygen for a predetermined period.

Potential redox indicators discussed in that application include indigotetrasulfonate, phenosafranine, methylene blue, diphenylamine,4′-ethoxy-2,4-diaminoazobenzene, diphenylamine sulfonic acid,diphenylbenzidine sulfonic acid, tris(2,2′-bipyridine)iron,tris(1,10-phenanthroline) iron (ferrion),tris(5-nitro-1,10-phenanthroline) iron and tris(2,2′-bipyridine)ruthenium. The preferred redox indicator discussed in that applicationis indigo tetrasulfonate (ITS).

A reduction reaction initiator initiates the reduction of the redoxindicator. An example of a reduction reaction initiator is titaniumdioxide. An electron donor donates electrons to the reduction reactioninitiator to allow for reduction of the redox indicator. Examples ofelectron donors include glycerol and sugars. In a preferred embodimentthe reduction reaction initiator is titanium dioxide and the electrondonor is glycerol.

Oxygen scavengers act to delay the oxidization of the redox indicator byreacting with oxygen before allowing the oxygen to react with the redoxindicator. Examples of oxygen scavengers include sodium bisulfate,ascorbic acid, iron (II) carbonate. Preferred oxygen scavengers aresodium bisulfate, ascorbic acid and iron (II) carbonate.

An indicator barrier agent acts to further delay the oxidization of theredox indicator by forming a physical or chemical barrier around it.Examples of indicator barrier agents include waxes that form a physicalbarrier around the redox indicator and polymers that encapsulate theredox indicator. A preferred indicator barrier agent is the polymerpoly(diallydimethylammonium chloride) also known as PDADMA. PDADMA actsto create a nanoreactor in the color changeable dye.

Other agents can be added to the color changeable dye in order to givethe dye physical properties that make it usable for its intendedpurpose. For example, a thickening agent can be added to the dye to giveit a workable consistency. A preferred thickening agent is2-hydroxyethyl cellulose.

As another example of an agent that gives the dye physical propertiesthat make it usable for its intended purpose, an agent to facilitatemixing lessens the tacky nature of the redox indicator and createsmicrospheres to help the hygroscopic glycerol mix with an aqueoussolvent and form a usable solution. Examples of agents to facilitatemixing include bentonite nanoclay, glass microspheres and celluloseacetate. A preferred agent to facilitate mixing is bentonite nanoclay.

An example of a color changeable dye that reacts based on carbon dioxidelevels in its environment could include a carbon dioxide reactive dyesuch as cresol red (CR, o-cresolsulfonephthalein) example formulation of1: cresol red, 20: glycerol, 3: 10M KOH (aq), Texas red hydrazide (THR),bromothymol blue (BTB, hydroxy triarylmethane), or m-cresol purple (MCP,hydroxyl triarylmethane). This carbon dioxide reactive dye could bemixed with a solvent such as alcohol, methanol or acetone. Bentonitenanoclay or diatomaceous earth could be added to give the colorchangeable dye desirable physical properties.

The carbon dioxide sensing color changeable dye could then be applied toa substrate. Examples of possible substrates include a sintered materialcomprised of plastic, metal or other such material, ahydroxyethyl-methacrylate substrate such as that used for hydrophiliccontact lenses (daily wear disposables) or a sponge that has beenextruded into a filament or a strip and then dipped into the carbondioxide color changeable dye.

The substrate with the carbon dioxide sensing color changeable dyethereon could then be laminated or encapsulated under a carbon dioxidecontrolled atmosphere (inclusion of or exclusion of carbon dioxide)between layers of plastic material such as Poly(vinyl chloride), (PVC),Polyethylene terephthalate (PET), or Saran having very low atmosphericdiffusion rates; thus forming an indicator strip. Additionally anadhesive back could be applied to the strip to form a sticker typeindicator. Under a carbon dioxide controlled atmosphere, the top of theindicator strip would be trimmed or cut off, thus presenting a smallatmospheric aperture to the extruded filament or strip.

The indicator strip could then be placed onto, within or around anydevice or into a package. The package would preferably be flood filledwith carbon dioxide. The package would be closed/sealed. Once thepackage was opened the indicator strip would be exposed to a low carbondioxide environment. This would trigger the indication of the carbondioxide sensing color changeable dye through the indicator substrate.

The indication timing control could be adjusted by adjusting the rate ofcarbon dioxide diffusion out of the indicator substrate, by decreasingthe diameter of the aperture thus lengthening the time of theindication, or by making the strip assembly longer. A combination ofadjustments such as length and aperture could also be used.

The interchangeable use protocol indicator can be provided in a numberof different ways. In one embodiment, the use protocol indicator(s) canbe incorporated into the disposable, limited or restricted use productitself. An interchangeable use protocol indicator that is incorporatedinto a product can be combined, inserted, joined or otherwise fixed intothe disposable, limited or restricted use product itself (e.g., by themanufacturer or the end user). In another, embodiment the use protocolindicator(s) can be disposed on the disposable, limited or restricteduse product. An interchangeable use protocol indicator that is disposedon a product is attached, affixed, adhered or otherwise fixed upon thedisposable, limited or restricted use product itself (e.g., by themanufacturer or the end user).

In yet another, embodiment the use protocol indicator(s) can providedwith but separate from the disposable, limited or restricted useproduct. In this last example, more than one use protocol indicator canbe provided allowing a user to select an appropriate use protocolindicator for an intended use protocol. For example, different useprotocol indicators could be provided in the packaging for a disposable,restricted or limited use medical device such as a feeding tube,catheter or connectors. The multiple use protocol indicators could beprovided in the form of adhesive use protocol indicators that can bedisposed on the medical device or a component such as plastic componentthat can be snapped into the medical device. The user could then selectthe use protocol indicator associated with the use protocol for which heor she intends to use the medical device. That use protocol indicatorcould be incorporated into the medical device or disposed on the medicaldevice. The medical device could then be used in the intendedenvironment. The color changeable dye on the use protocol indicatorwould then change color at the defined time after which the medicaldevice should no longer be used for that particular use protocol. Asanother example, multiple adhesive use protocol indicators could beincluded in a package with a medication that has a different shelf lifebased on different uses. The user could then select the adhesive useprotocol indicator appropriate for his or her intended use and attach itto the packaging for the medication. The use protocol indicator wouldthen change color at the time after which the medication should nolonger be used for that particular intended use.

In yet another embodiment, more than one interchangeable use protocolindicators are included in a kit. The interchangeable use protocolindicators do not have to be provided with a disposable, limited orrestricted use product. They can be appropriate for use with numerousdisposable, limited or restricted use products. For example, a kit ofadhesive interchangeable use protocol indicators, such as stickers,could be provided with different color change times, e.g., 1 day, 3days, 5 days, one week, etc. The user could then apply the adhesiveinterchangeable use protocol indicators on products, e.g., food items ina refrigerator based on the best buy date. In another example, theinterchangeable use protocol indicators could be elastic loops, such asrubber bands, that could be wrapped around various products. Asdiscussed above, the use protocol indicator(s) can be incorporated intothe disposable, limited or restricted use product. The use protocolindicator(s) can be a portion of the disposable, limited or restricteduse product having an appearance indicative of the use protocol forwhich the disposable, limited or restricted use product is intended. Forexample, the use protocol indicator(s) can be a portion of thedisposable, limited or restricted use product having a particular colorassociated with a particular use protocol.

In one embodiment, the color changeable dye is disposed on the useprotocol indicator. The dye can be directly disposed onto the useprotocol indicator. The dye can also be indirectly disposed on the useprotocol indicator. For example, the color changeable dye can bedisposed on an adhesive label on the use protocol indicator. In anotherembodiment, the color changeable dye is incorporated into the useprotocol indicator itself.

FIG. 1 is a schematic drawing of one embodiment of the present inventionshowing a medical device 100 having a use protocol indicator 102 with acolor changeable dye incorporated therein. The use protocol indicator102 is a plastic colored, interchangeable ring indicative of the useprotocol for which the medical device is intended. For example, a firstcolor is indicative that the medical device is intended for a first useprotocol, a second color is indicative that the medical device isintended for a second use protocol, and a third color is indicative thatthe medical device is intended for a third use protocol.

As discussed above, the medical device can be provided with the coloredcomponent(s) already incorporated into the medical device to indicate itis intended for a certain use protocol (e.g., by the manufacturer).Alternatively, multiple interchangeable colored attachable componentscan be provided in the packaging with the medical device for insertion,connection or attachment by the user. The components can each have acolor changeable dye that changes color after an amount of time in acertain environment associated with a particular use protocol. The usercan then select the component associated with the particular useprotocol for which he or she intends to use the medical device.

As discussed above the color changeable dye can be disposed on orincorporated into the use protocol indicator. In an embodiment, aplastic colored portion is a multi-layer polymer with the colorchangeable dye incorporated therein. In yet another embodiment a portionhas a capillary with the color changeable dye incorporated therein. FIG.2 is a schematic drawing of one embodiment of the present inventionshowing an interchangeable component 200 with a capillary 202 containinga color changeable dye 204. The capillary 202 is incorporated into theinterchangeable component 200. The capillary 202 can be a metal orplastic material. The capillary 202 has an aperture 206 that allows theenvironmental conditions to which the color changeable dye responds toaccess the color changeable dye 204. This controls the manner in whichthe environment conditions contact the color changeable dye 204. Forexample, where the color changeable dye 204 is an oxygen sensing colorchangeable dye. The aperture 206 controls the flow of oxygen to the dye.The color change of the dye can be delayed and/or controlled in thismanner. Moreover, additional barrier materials may be incorporated intothe capillary to further delay the color change of the dye.

FIG. 3 is a schematic drawing of one embodiment of the present inventionshowing use adhesive protocol indicators for use with a medical device.The medical device 300 and a sheet of adhesive use protocol indicators302 are packaged together in a sterile environmentally-controlledpackage 304, for example, carbon dioxide or inert gas. When the useropens the package 304, he or she exposes the adhesive use protocolindicators 302 and the medical device 300 to the intended useenvironment. The user can then select the adhesive use protocolindicators associated with the use protocol for which he or she intendsto use the medical device 300. The selected adhesive use protocolindicators will then change color at the defined time after which themedical device 300 should no longer be used for the particular protocolselected by the user. The color changeable dye can be disposed on orincorporated into the adhesive use protocol indicators.

The present application also involves a method for using interchangeableuse protocol indicators. The method involves providing a disposable,limited or restricted use product having more than one use protocol withmore than one associated use protocol indicators with the colorchangeable dye and selecting at least one use protocol indicator.

Another embodiment of the present application deals with providing anexposure time indicator scale that indicates how long a disposable,restricted or limited use product has been exposed to a certainenvironment and the time remaining before the disposable, restricted orlimited use product should no longer be used. In other words, theexposure time indicator reflects a continuum reflecting the time passedand time remaining for the product. Such an apparatus comprises adisposable, limited or restricted use product and an exposure timeindicator. The exposure time indicator comprises at least one colorchangeable dye. The at least one color changeable dye is translucent,milky white or has a first color upon immediate exposure to anenvironment and the dye changes color after exposure to the environment.The at least one color changeable dye is disposed in such a manner tocreate a sequential color change that indicates how long the disposable,restricted or limited use product has been exposed to a certainenvironment and the time remaining before the disposable, restricted orlimited use product should no longer be used. The user would not simplyknow whether a product had reached its expiration date but how long heor she has until it reaches that date.

One example where this might be useful is a feeding tube that should bereplaced after approximately one week. A hospital worker could see theexposure time indicator scale and determine when the feeding should bechanged. Another example, of the usefulness of the exposure timeindicator could be in determining expiration dates on food. Otherexamples of products where such an indication could prove useful arecosmetic products, personal hygiene products such as electric toothbrushheads, and home diagnostic kits such as pregnancy tests and ovulationprediction tests. In each of these examples, the exposure time indicatorallows the user to better plan for change or removal of the product byindicating how long the user has until the product reaches itsexpiration time.

FIG. 4 is a schematic drawing of one embodiment of the present inventionshowing an exposure time indicator with a color changeable dye thatchanges color after exposure to an environment in a sequential manner.The exposure time indicator has a first region of a color changeable dye402 that changes color after a first time, consecutive regions of acolor changeable dye 404 that change color at increasing time intervalsafter the first time and a final region 406 of a color changeable dyethat changes color after a final defined time. The final defined timecorresponds to a time after which the disposable, limited or restricteduse product should not be used.

The color changeable dye can be varied in order to change color inresponse to a variety of different environments for a defined time forexample as discussed above. In a preferred embodiment the environment isan oxygen containing environment and the color changeable dye is anoxygen sensing color changeable dye. In another preferred embodiment theenvironment is a carbon dioxide containing environment and the colorchangeable dye is a carbon dioxide sensing color changeable dye. Theenvironment to which the color changeable dye responds can be chosenbased on the environment in which the disposable, limited or restricteduse product is intended to be used.

In order to create dyes that change color after exposure to differentenvironment after different periods of time there are a number ofpossible approaches as discussed above. In order to create dyes thatchange color after exposure to different environment after differentperiods of time there are a number of possible approaches. Dyes thathave completely different compositions can be used. Variations in themakeup of the dye can be used. Scavenger, such as oxygen scavengers, canbe added. Barriers can be also be added. Some examples of colorchangeable dyes using these approaches to achieve color change atdifferent times or in response to different atmospheres were discussedabove are equally applicable to this embodiment.

Examples of a color changeable dye that reacts based on carbon dioxidelevels in its environment are described above.

Barriers can also be used to achieve the extended sequential colorchange of the present exposure time indicator. Physical polymer barrierscan be applied over the color changeable dye in a stepwise fashion tocreate a sequential color change. A color changeable dye such as thosedescribed above can be disposed onto a substrate, such as a paperindicator strip. Polymer sheets, such as polypropylene, are thendisposed on top of the color changeable dye. The polymeric sheets inthis can be disposed with no sheets on the first region, one sheet on asecond region, two sheets on a third region, three sheets on a fourthregion and so on. Single sheets of increasing thickness can also beused.

FIGS. 5A-L are photographs of an exposure time indicator utilizingstepped polymeric barriers with a color changeable carbon dioxidesensing dye (as described above) that changes color in a sequentialmanner after being removed from a carbon dioxide rich environment andexposed to the intended use environment, e.g., an atmosphericenvironment. The stepped polymer sheets adhered over the paper indicatorstrip in the example are 0.002 inch thick cellulose. This device hasnine regions with no sheets in the first region, one sheet in the secondregion, two sheets in the third region and so on. The region with nopolymeric strips changes color in a matter of minutes. This can be seenin FIGS. 5A-5D. This rapid change indicates that the test strip isworking and has been activated. Each 0.002 inch thick cellulose layerprovides about a 2 hour barrier for the color changeable dye. The regionwith one strip changes color after approximately 2 hours, the regionwith two strips after approximately 4 hours and so on in a controlledsequential manner. This can be seen in FIGS. 5E-5K. The final region has8 strips and changes after approximately 16 hours. This can be seen inFIG. 5L. This sequential change allows a user to ascertain the time thathas elapsed since the disposable, limited or restricted use product hasbeen opened and to anticipate the remaining time before replacement isrequired.

More sheets or thicker sheets will extend the indication time.Conversely, fewer sheets or thinner sheets will decrease the indicationtime. Additionally using a material that has a higher or lower diffusionof gas will also shorten or lengthen the time respectively. For example,Mylar and Teflon have high low diffusion rates for gases and wouldlengthen the time before color change of the color changeable dye.Polyethylene has a high diffusion rate for gases and would shorten thetime before color change of the color changeable dye. Different gaseswould also diffusion through the barriers at different rates. Forexample, carbon dioxide is a smaller molecule and would diffuse throughmore quickly. The time change can further be timed using thisinformation.

The exposure time indicator can be provided in a number of differentways. In one embodiment, the exposure time indicator can be incorporatedinto the disposable, limited or restricted use product itself. Inanother embodiment, the exposure time indictor can be disposed directlyon the disposable, limited or restricted use product. In anotherembodiment, the exposure time indicator can also be indirectly disposedon the disposable, limited or restricted use product. For example, theexposure time indicator can be disposed on an adhesive label on thedisposable, limited or restricted use product. In yet another,embodiment the exposure time indicator can provided with but separatefrom the disposable, limited or restricted use product. Alternatively,the exposure time indicator(s) can be provided independently such that auser can use the indicator on a variety of different products.

As discussed above, the exposure time indicator can be incorporated intothe disposable, limited or restricted use product. The exposure timeindicator can be incorporated into a portion of the disposable, limitedor restricted use product and in conjunction with the use protocolindicator described above. In another embodiment, a plastic portion is amulti-layer polymer with the color changeable dye incorporated therein.

In yet another embodiment a component has a capillary with the colorchangeable dye incorporated therein. As described above, FIG. 2 is aschematic drawing of one embodiment of the present invention where theexposure time indicator could be used. Specifically, the color changecan be controlled to proceed in a sequential manner using the exposuretime indicator. The color change can move in a continuum around thecapillary in a sequential manner through a first region, consecutiveregions and a final region to indicate the time passed and time untilwhich the disposable, limited or restricted use product should no longerbe used. Moreover, additional barrier materials may be incorporated intothe capillary to further delay the color change of the dye.

While the application has been described with reference to certainembodiments, it will be understood by those skilled in the art thatvarious changes may be made and equivalents may be substituted withoutdeparting from the scope of the application. In addition, manymodifications may be made to adapt a particular situation or material tothe teachings of the application without departing from its scope.Therefore, it is intended that the application not be limited to theparticular embodiment disclosed, but that the application will includeall embodiments falling within the scope of the appended claims.

The invention claimed is:
 1. An apparatus with time controlled colorchange indication comprising: a packaging comprising a carbon dioxiderich environment; a medical device disposed in the packaging; a colorchange indicator disposed on the medical device, the indicatorcomprising at least one carbon dioxide sensing color changeable dyedisposed on a substrate and wherein the indicator is laminated with oris encapsulated between layers of permeable plastic material wherein theplastic material is configured to control the rate of carbon dioxidediffusion through the plastic material and wherein the indicator isconfigured to change color after a predetermined time that correspondsto an intended use time of the medical device.
 2. The apparatus of claim1 wherein the dye comprises cresol red, thymol blue, or m-cresol purple.3. The apparatus of claim 1 wherein the color change indicator comprisesmore than one dye.
 4. The apparatus of claim 1 wherein the indicator isencapsulated between layers of plastic material and wherein the plasticmaterial are selected from the group of polyvinyl chloride, polyethyleneterephthalate, or Saran.
 5. An apparatus with time controlled colorchange indication comprising: a medical device comprising a color changeindicator, the color change indicator comprising at least one carbondioxide sensing color changeable dye and a permeable polymeric barrierdisposed on top of said dye wherein the polymeric barrier is configuredto control the rate of carbon dioxide diffusion through the barrier todelay color change of said dye for a predetermined period of time thatcorresponds to an intended use time of the medical device.
 6. Theapparatus of claim 5 wherein the dye comprises cresol red, thymol blue,or m-cresol purple.
 7. The apparatus of claim 5 wherein the color changeindicator comprises more than one carbon dioxide sensing colorchangeable dye.
 8. The color changeable dye of claim 5 where saidpolymeric barrier is comprised from at least one of the group comprisingpolyethylene, cellulose, Mylar, or Teflon.
 9. An apparatus with timecontrolled color change indication, the apparatus comprising: a medicaldevice comprising an exposure time indicator comprising at least onecarbon dioxide sensing color changeable dye and a plurality of permeablepolymeric barriers applied over the dye and configured to control therate of carbon dioxide diffusion through the polymeric barriers; andwherein the polymeric barriers are configured to allow a portion of theindicator to change color in a sequential manner and wherein a firstregion of the indicator changes color at a first predetermined time anda final region changes color after a final predetermined time thatcorresponds to an intended use time of the medical device.
 10. Theapparatus of claim 9 wherein the indicator further comprises a capillarywith the color changeable dye incorporated therein.
 11. The apparatus ofclaim 9 wherein the plurality of polymeric barriers comprises steppedpolymer sheets and wherein the first region has no polymeric barrierdisposed thereon and changes color within minutes after exposure toatmospheric conditions.
 12. The apparatus of claim 9 wherein theexposure time indicator is incorporated into the medical device.
 13. Theapparatus of claim 9 wherein the exposure time indicator is directly orindirectly disposed on the medical device.
 14. The apparatus of claim 9wherein the dye comprises cresol red, thymol blue, or m-cresol purple.